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WO1996012719A1 - Derive de quinoline - Google Patents

Derive de quinoline Download PDF

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Publication number
WO1996012719A1
WO1996012719A1 PCT/JP1995/002167 JP9502167W WO9612719A1 WO 1996012719 A1 WO1996012719 A1 WO 1996012719A1 JP 9502167 W JP9502167 W JP 9502167W WO 9612719 A1 WO9612719 A1 WO 9612719A1
Authority
WO
WIPO (PCT)
Prior art keywords
phenyl
methyl
carbon atoms
quinolyl
group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP1995/002167
Other languages
English (en)
Japanese (ja)
Inventor
Yutaka Nomura
Shogo Sakuma
Seiichiro Masui
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nippon Chemiphar Co Ltd
Original Assignee
Nippon Chemiphar Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nippon Chemiphar Co Ltd filed Critical Nippon Chemiphar Co Ltd
Priority to EP95934864A priority Critical patent/EP0787725B1/fr
Priority to DE69530501T priority patent/DE69530501D1/de
Priority to AT95934864T priority patent/ATE238297T1/de
Priority to RU97107992/04A priority patent/RU2137770C1/ru
Priority to KR1019970702575A priority patent/KR100356551B1/ko
Priority to US08/809,592 priority patent/US5693651A/en
Priority to AU37098/95A priority patent/AU712802B2/en
Publication of WO1996012719A1 publication Critical patent/WO1996012719A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • the present invention relates to a quinoline derivative having a hypoglycemic effect.
  • an insulin preparation as an injection or a sulfonyl urine such as a biguanide such as metformin hydrochloride and tolutamide as an oral preparation have been used.
  • a biguanide such as metformin hydrochloride and tolutamide
  • insulin preparations are cumbersome to use due to injections, while biguanides, which are orally administered, cause lactic acidosis, and sulfonylureas have the side effect of severe hypoglycemia.
  • troglitazone trog li tazone: European Patent No.
  • Troglitazone hydrochloride pioglitazone hydrochloride (pi og lit azon e), which has a new mechanism of action to improve dysfunction of insulin (insulin resistance) which does not have these disadvantages, has been developed.
  • Hydrochloride European Patent No. 193,256 and the like, and 5-substituted benzylthiazolidine-1, 4-dione derivatives have attracted attention.
  • Troglitazone has a hypoglycemic effect and a neutral flour fat-reducing effect, improves impaired insulin receptor function, also acts on glucose transporters and glucokinase, and impairs insulin action. It is said to improve.
  • An object of the present invention is to provide a novel quinoline derivative having a hypoglycemic action.
  • an object of the present invention is to provide a novel quinoline derivative having a hypoglycemic effect by oral administration.
  • R 1 is hydrogen, an alkyl group having 1 to 6 carbon atoms, -NR 4 R s (R 4 and R 5 are each independently of one another, hydrogen, alkyl having 1 to 6 carbon atoms, phenyl, pyridyl, pyrimidyl, Or a benzoyl) amino group, or as a substituent, alkyl having 1 to 6 carbons, alkoxy having 1 to 6 carbons, halogen, hydroxy, halogenoalkyl having 1 to 6 carbons, or 1 to 6 carbons
  • R 2 is hydrogen, an alkyl group having 1 to 6 carbon atoms, -NR 6 ′ R 7 (R 6 and R 7 are independently of each other, hydrogen, alkyl having 1 to 6 carbon atoms, phenyl, pyridyl, pyrimidyl Or a benzoyl) amino group, or a C1-C6 alkyl, a C1-C6 alkoxy, a halogen, a hydroxy, a C1-C6 halogenoalkyl, a C1-carbon A phenyl group, a naphthyl group, a cycloalkyl group having 3 to 8 carbon atoms, or a ring-forming atom, which may have a halogenoalkoxy, nitro, amino, phenyl, phenyl, phenyl, thiazolyl, or pyridyl group Represents a 5- to 8-membered complex group consisting of 1 to 2 nitrogen, oxygen, or sulfur
  • the quinoline derivative represented by the formula is preferred.
  • the quinoline derivative of the present invention includes the following general formula (m):
  • R 3 is a substituent having 1 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, halogen, hydroxy, halogenoalkyl having 1 to 6 carbon atoms, halogenoalkoxy having 1 to 6 carbon atoms, nitro, A phenyl, oxazolyl, or pyridyl group which may have an amino, phenyl, phenyl, thienyl, furyl, thiazolyl or pyridyl group, and k represents an integer of 0-4.
  • the quinoline derivative represented by is preferred.
  • C1-C6 alkyl groups eg, methyl, ethyl, propyl, and isobutyl
  • R 5 or —NR e R 7 R 4 , R 5 , R 6 , and R 7 may be the same or different from each other. It is selected from hydrogen, alkyl having 1 to 6 carbon atoms (eg, methyl, ethyl, propyl, and isopropyl), phenyl, pyridyl, pyrimidyl, or benzoyl. In addition, these alkyl, phenyl, pyridyl, pyrimidyl, and benzoyl may have a substituent.
  • Phenyl, naphthyl, cycloalkyl group having 3 to 8 carbon atoms eg, cyclohexyl, cyclopentyl
  • ⁇ -forming atom consisting of 1 to 2 nitrogen, oxygen, or sulfur and the remaining number of carbon atoms 5- to 8-membered heterocyclic groups (eg, pyridyl, thiazolyl, oxazolyl, chenyl, furyl, pyrrolyl, morpholinyl, indolyl, imidazolyl, biberidinyl).
  • all of these phenyl, naphthyl, cycloalkyl and heterocyclic groups have 1 or 2 or more alkyl having 1 to 6 carbons as substituents (eg, methyl, ethyl, brovir, and Isopropyl) “alkoxy having 1 to 6 carbon atoms (eg, methoxy, ethoxy, and propoxy, isopropoxy), halogen (eg, chlorine, fluorine, bromine), hydroxy, halogenoalkyl having 1 to 6 carbon atoms (eg, 2 —Chloroethyl, trifluoromethyl), halogenoalkoxy with 1 to 6 carbon atoms (eg, 2 —chloroethoxy), nitro, amino (eg, NH 2 , methylamino, methylamino, dimethylamino, getylamino), phenyl, chenyl, frill , Thiazolyl, or pyridyl may also be
  • Phenyl, oxazolyl, pyridyl is, as a substituent, 1 or 2 or more alkyl having 1 to 6 carbons (eg, methyl, ethyl, propyl, and isopropyl), and alkoxy having 1 to 6 carbons (eg, Methoxy, ethoxy, and propoxy, isobroboxy), halogen (eg, chlorine, fluorine, bromine), hydroxy, halogenoalkyl having 1 to 6 carbon atoms (eg, 2-chloroethyl, trifluoromethyl), 1 to 1 carbon atoms 6 may have a halogenoalkoxy (eg, 2-chloro ethoxy), nitro, amino (eg, NH 2 , methylamino, ethylamino, dimethylamino, getylamino), phenyl,
  • alkyl having 1 to 6 carbons eg, methyl, ethyl, propyl,
  • S sulfur or 0 (oxygen).
  • oxygen preferably it is S.
  • P and q are preferably 0. m, n, and k are preferably 1 or 2.
  • the quinoline ring is also substituted with an alkyl having 1 to 6 carbon atoms such as methyl, ethyl and butyl, and an alkoxy having 1 to 6 carbon atoms such as methoxy and ethoxy. It may have a substituent such as halogen such as chlorine and fluorine.
  • a group bonded to the pyridine ⁇ moiety of quinoline ⁇ such as thiazolidine-1,2,4-dione-15-ylmethyl, and R 1 — (CH 2 ) Pyridine groups attached to benzene ring portion of the ring, such as m one Z- (CH 2) p scratch, as seen in the general formula (m), respectively 3-position of the reluctant down ring, 7 It is preferable to bond at the position.
  • the quinoline derivative of the present invention may exist as a pharmacologically acceptable salt.
  • a salt include an acid salt with an organic or inorganic acid such as hydrochloric acid or acetic acid, or an alkali metal (eg, , Sodium and potassium) and the like.
  • an asymmetric carbon is present at the 5-position of the thiazolidine-1,2,4-dione ring of the quinoline derivative of the present invention, the quinoline derivative of the present invention includes an optically active compound, Racemic compounds are also included.
  • the quinoline derivative represented by the above general formula (m) of the present invention can be obtained by, for example, the following production method (synthesis method 11).
  • 3-nitro-7-hydroxyquinoline of the formula (a) is used for the reaction of dimethylformamide (DMF), benzene, toluene, dichloromethane, pyridine, tetrahydrofuran (THF), dimethylsulfoxide (DMSO), etc.
  • a halogen compound of the formula (b) is reacted in the presence of a base such as sodium hydride, sodium alkoxide, triethylamine, sodium hydroxide, sodium carbonate, etc. —Ditroquinoline derivative power is obtained.
  • the 3-ditroquinoline derivative of the formula (c) is catalytically reduced using platinum oxide, palladium carbon, or the like in a solvent that does not participate in a reaction such as ethanol, ethyl acetate, methanol, or THF, or iron or zinc and acetic acid.
  • a solvent that does not participate in a reaction such as ethanol, ethyl acetate, methanol, or THF, or iron or zinc and acetic acid.
  • reduction using tin chloride (II) is performed to obtain the 3-aminoquinoline derivative of formula (d).
  • the 3-aminoquinoline derivative of the formula (d) is reacted with sodium nitrite in a solvent that does not participate in the reaction of acetone, methanol, or the like, in the presence of a hydrohalic acid such as aqueous hydrogen sulfide or concentrated hydrochloric acid.
  • a hydrohalic acid such as aqueous hydrogen sulfide or concentrated hydrochloric acid.
  • the 2-halogeno-3-quinolyl brobionate of the formula (e) is converted to a solvent such as ethanol, 2-methoxyethanol, methanol, propanol, or isopropanol which does not participate in the reaction in the presence of sodium acetate.
  • a solvent such as ethanol, 2-methoxyethanol, methanol, propanol, or isopropanol which does not participate in the reaction in the presence of sodium acetate.
  • thiourea to give a 2-iminothiazolidine-14-one derivative of formula (f).
  • a 2-iminothiazolidine-14-one derivative of the formula (f) is used, for example, in a mixed solution of an inorganic acid and an alcohol (examples of inorganic acids: hydrochloric acid, sulfuric acid, hydrogen bromide, examples of alcohol: ethanol) , Methanol, propanol and isopropanol) to obtain a quinoline derivative of the general formula (ffl).
  • the quinoline derivative represented by the general formula (m) can also be obtained by the following production method (synthesis method 1).
  • G represents a leaving group such as chlorine, bromine, iodine, mesyloxy, trisyloxy, etc.
  • M represents an alkali metal such as lithium, sodium, potassium, etc.
  • R 3 and n are the same as those described above. Meaningful
  • the quinoline derivative represented by the general formula (m) can also be obtained by the following production method (synthesis method-3).
  • the 3-formylquinoline derivative is dehydrated and condensed with thiazolidin-1,2,4-dione in the presence of a base such as biveridine, piperazine, triethylamine, and soda carbonate using the synthesis method 13.
  • a base such as biveridine, piperazine, triethylamine, and soda carbonate
  • a quinoline derivative represented by the general formula (() thiazolidine-1-5-indene type
  • a quinoline derivative represented by the general formula ( ⁇ ) can be obtained. .
  • the quinoline derivative represented by the general formula (ffl) can also be obtained by the following production method (synthesis method 14).
  • a 7-hydric xyquinoline derivative and, for example, benzyl alcohol (R 3 — (CH 2 ) ⁇ -OH) were mixed with THF as a solvent and triphenylphenylphosphine (PPh
  • the quinoline derivative of the general formula (ffl) can be obtained by treating with 3 ) and acetyl dicarboxylate (DEAD) (Mitsunobu reaction).
  • KK Ay mice a model animal of inulin-independent diabetes.
  • KK Ay mice (9-11 weeks old) were divided into homogeneous groups according to plasma glucose concentration, and then suspended in a 1% methylcellulose solution (the quinoline derivative synthesized in each Example described below) and Bioglitazone (comparative compound) was orally administered once a day for 3 days.
  • a 1% methylcellulose solution was orally administered to the control (drug-free group). Blood was collected 18 hours after the last administration, and the plasma glucose concentration was measured.
  • the measurement was performed by an automatic analyzer (Type 705, manufactured by Hitachi, Ltd.) by an enzyme method using Autocera GLU (Daiichi Pure Chemicals Co., Ltd.).
  • the plasma glucose concentration of each compound administration group was determined, and the ratio (percent) of the value to the control was calculated. The results are shown in Table 1.
  • test compound was suspended in a 1% aqueous solution of methylcellulose, and the suspension was fed with a CRF-solid sample (manufactured by Oriental Yeast Co., Ltd.) and water freely.
  • Cr j CD (Sprague-Dawley) system rat ( Female, 5 weeks old, 5 animals per group) 1 daily Gavage over 4 weeks.
  • the dose of the test compound was SOOmgZkg gZ day and 600mg / kgZ day for the compound of the present invention (Example 6), and 200mgZkgZ day for bioglitazone (bioglitazone hydrochloride: comparative compound).
  • the quinoline derivative of the present invention can be administered either orally or parenterally.
  • Oral dosage forms include tablets, capsules, powders, granules and scillos.
  • Parenteral administration methods include mucosal administration such as eye drops, inhalants, propellants, suppositories, etc. Examples include body surface administration of ointments and the like, and intravascular and tissue administration of injections and the like.
  • the above oral preparations are produced using ordinary excipients, disintegrants, binders, lubricants, pigments, diluents and the like.
  • Excipients include glucose and lactose; disintegrants include hard powder, calcium carboxymethylcellulose; lubricating agents include magnesium stearate, talc; and binding agents include hydroxypropyl cellulose.
  • disintegrants include hard powder, calcium carboxymethylcellulose; lubricating agents include magnesium stearate, talc; and binding agents include hydroxypropyl cellulose.
  • lubricating agents include magnesium stearate, talc; and binding agents include hydroxypropyl cellulose.
  • binding agents include hydroxypropyl cellulose.
  • Gelatin, polyvinylpyrrolidone and the like are used.
  • parenteral preparations and injections they are prepared using distilled water for injection, physiological saline, and Ringer's solution.
  • the dosage of the quinoline derivative of the present invention is usually about 0.1 mg to 200 mg per day for injection and about 1 mg to 200 mg per day for oral administration for adults. It can be increased or decreased depending on species, symptoms, etc.
  • the quinoline derivative of the present invention has an excellent hypoglycemic effect and is low in toxicity, so that it is useful as a therapeutic agent for diabetes, particularly for oral administration.
  • 3-Amino-7- (2-trifluoromethylbenzyloxy) quinoline (60 Omg, 1.9 mmol) is dissolved in a mixed solvent of acetone and methanol (1.76 mLZ 4.46 mL), and 47% hydrogen bromide is dissolved. Water (1.35 g) was added.
  • the ®® was separated, washed with water, and washed with sodium sulfate! ⁇ .
  • the solvent was distilled off under reduced pressure to give 300 mg of the title compound as a crude product in the residue.
  • the crude product was used in the next step without purification of [il ⁇ ].

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Endocrinology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des dérivés représentés par un nouveau dérivé de thiazolidine-2,4-dione ne présentant pas de groupe benzyle en position 5, lequel est représenté par la formule générale (I) et présente un effet hypoglycémique, et notamment de nouveaux dérivés de quinoline présentant un effet hypoglycémique lorsqu'on les administre par voie orale. Dans ladite formule (I) R1 représente hydrogène, alkyle C¿1?-C6, amino représenté par NR?4R5 (R4 et R5¿ représentant indépendamment hydrogène, alkyle C¿1?C6, phényle, pyridile, pyrimidyle ou benzoyle), phényle, naphtyle ou cycloalcyle C3-C8 pouvant être substitués par alkyle C1-C6, alcoxy C1-C6, halogéno, hydroxy, halogénoalkyle C1-C6, halogénoalcoxy C1-C6, nitro, amino, phényle, thiényle, furyle, thiazolyle ou pyridyle, ou un groupe hétérocyclique renfermant cinq à huit éléments présentant un ou deux atomes d'azote, d'oxygène ou de soufre, le reste étant constitué d'atomes de carbone en tant qu'atomes constitutifs du noyau; Z représente O, S, C=O ou CH2; E représente S ou O; m représente un nombre entier compris entre 0 et 4; p représente un nombre entier compris entre 0 et 4; q représente un nombre entier compris entre 0 et 4; et -- représente une liaison simple ou double.
PCT/JP1995/002167 1994-10-20 1995-10-20 Derive de quinoline Ceased WO1996012719A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP95934864A EP0787725B1 (fr) 1994-10-20 1995-10-20 Derive de quinoline
DE69530501T DE69530501D1 (de) 1994-10-20 1995-10-20 Chinolinderivat
AT95934864T ATE238297T1 (de) 1994-10-20 1995-10-20 Chinolinderivat
RU97107992/04A RU2137770C1 (ru) 1994-10-20 1995-10-20 Производные хинолина
KR1019970702575A KR100356551B1 (ko) 1994-10-20 1995-10-20 퀴놀린유도체
US08/809,592 US5693651A (en) 1994-10-20 1995-10-20 Quinoline derivatives
AU37098/95A AU712802B2 (en) 1994-10-20 1995-10-20 Quinoline derivatives

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP6/281301 1994-10-20
JP28130194 1994-10-20
JP21805695 1995-08-03
JP7/218056 1995-08-03

Publications (1)

Publication Number Publication Date
WO1996012719A1 true WO1996012719A1 (fr) 1996-05-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1995/002167 Ceased WO1996012719A1 (fr) 1994-10-20 1995-10-20 Derive de quinoline

Country Status (10)

Country Link
US (1) US5693651A (fr)
EP (1) EP0787725B1 (fr)
KR (1) KR100356551B1 (fr)
CN (1) CN1071333C (fr)
AT (1) ATE238297T1 (fr)
AU (1) AU712802B2 (fr)
CA (1) CA2201113A1 (fr)
DE (1) DE69530501D1 (fr)
RU (1) RU2137770C1 (fr)
WO (1) WO1996012719A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998020871A1 (fr) * 1996-11-08 1998-05-22 Nippon Chemiphar Co., Ltd. Agent diminuant la graisse viscerale
WO2004074284A1 (fr) * 2003-02-21 2004-09-02 Pfizer Inc. Derives d'oxazole utilises en tant qu'agonistes de ppar
JP2010511608A (ja) * 2006-11-30 2010-04-15 ダウ アグロサイエンシィズ エルエルシー ２−置換−５−（１−アルキルチオ）アルキルピリミジンの製造方法

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000073273A1 (fr) * 1999-05-28 2000-12-07 Nippon Chemiphar Co., Ltd. Procede d'obtention de derives 2-halo-3-(3-quinolyl) acide proprionique
WO2002051441A1 (fr) * 2000-12-26 2002-07-04 Sankyo Company, Limited Compositions medicinales contenant un diuretique et un agent renforçant la resistance a l'insuline
US7015345B2 (en) * 2002-02-21 2006-03-21 Asahi Kasei Pharma Corporation Propionic acid derivatives
US20050119314A1 (en) * 2002-04-05 2005-06-02 Sankyo Company, Limited Pharmaceutical composition comprising an ACAT inhibitor and an insulin resistance reducing agent
US7232828B2 (en) 2002-08-10 2007-06-19 Bethesda Pharmaceuticals, Inc. PPAR Ligands that do not cause fluid retention, edema or congestive heart failure
US7241893B2 (en) * 2004-09-17 2007-07-10 Hoffman-La Roche Inc. Thiazolinone 2-substituted quinolines
US7253285B2 (en) * 2004-09-17 2007-08-07 Hoffmann-La Roche Inc. Thiazolinone 4-monosubstituted quinolines
WO2008020302A2 (fr) * 2006-08-17 2008-02-21 Pfizer Products Inc. Composés hétéro-aromatiques à base de quinoline
JP5793505B2 (ja) 2009-12-23 2015-10-14 ジャスコ ファーマシューティカルズ， エルエルシー アミノピリミジンキナーゼ阻害薬
WO2012145617A2 (fr) * 2011-04-22 2012-10-26 Jasco Pharmaceuticals, LLC Inhibiteurs d'aminopyrimidine kinase
CA2853454C (fr) 2011-11-04 2020-01-21 Jasco Pharmaceuticals, LLC Inhibiteurs d'aminopyrimidine kinase

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61267580A (ja) * 1985-01-19 1986-11-27 Takeda Chem Ind Ltd チアゾリジン誘導体

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL106877A (en) * 1992-09-10 1998-03-10 Lilly Co Eli Rhodanine derivatives for use as medicaments for the treatment of alzheimer's disease
FR2696743B1 (fr) * 1992-10-12 1994-12-23 Adir Nouveaux composés de thiazolidine dione, leur procédé de préparation et les compositions pharmaceutiques les contenant.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61267580A (ja) * 1985-01-19 1986-11-27 Takeda Chem Ind Ltd チアゾリジン誘導体

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998020871A1 (fr) * 1996-11-08 1998-05-22 Nippon Chemiphar Co., Ltd. Agent diminuant la graisse viscerale
US6121288A (en) * 1996-11-08 2000-09-19 Nippon Chemiphar Co., Ltd. Visceral fat lowering agent
WO2004074284A1 (fr) * 2003-02-21 2004-09-02 Pfizer Inc. Derives d'oxazole utilises en tant qu'agonistes de ppar
JP2010511608A (ja) * 2006-11-30 2010-04-15 ダウ アグロサイエンシィズ エルエルシー ２−置換−５−（１−アルキルチオ）アルキルピリミジンの製造方法
JP2013056912A (ja) * 2006-11-30 2013-03-28 Dow Agrosciences Llc ２−置換−５−（１−アルキルチオ）アルキルピリミジンの製造方法

Also Published As

Publication number Publication date
EP0787725B1 (fr) 2003-04-23
EP0787725A1 (fr) 1997-08-06
ATE238297T1 (de) 2003-05-15
CA2201113A1 (fr) 1996-05-02
EP0787725A4 (fr) 1998-01-07
US5693651A (en) 1997-12-02
CN1071333C (zh) 2001-09-19
KR100356551B1 (ko) 2002-12-18
CN1170411A (zh) 1998-01-14
DE69530501D1 (de) 2003-05-28
RU2137770C1 (ru) 1999-09-20
AU712802B2 (en) 1999-11-18
AU3709895A (en) 1996-05-15
KR970707122A (ko) 1997-12-01

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